A 58-year-old man from rural India presents with progressive dysphagia and weight loss over 6 months. Upper endoscopy reveals a poorly differentiated adenocarcinoma of the gastric antrum with invasion into the muscularis propria. CT staging shows no distant metastases. He undergoes subtotal gastrectomy with D2 lymphadenectomy. What is the drug of choice for adjuvant chemotherapy in this patient?

## Adjuvant Chemotherapy for Resected Gastric Cancer ### Standard of Care **Key Point:** For resected gastric cancer (post-D2 gastrectomy), the landmark ACTS-GC trial established **S-1 (tegafur/gimeracil/oteracil)** as the standard in Japan/Asia, while in Western practice the **MacDonald regimen (5-Fluorouracil + Leucovorin + radiation)** or **FLOT/FOLFOX** are used. Among the options provided, **5-Fluorouracil with Leucovorin** (the Macdonald/INT-0116 regimen) has the strongest level-1 evidence for adjuvant therapy in resected gastric cancer. ### Evidence Base - **INT-0116 (MacDonald) Trial (NEJM 2001):** Adjuvant chemoradiation with **5-FU + Leucovorin** significantly improved overall survival (median OS 36 vs 27 months) and disease-free survival compared to surgery alone after curative resection of gastric/GEJ adenocarcinoma. This remains a cornerstone reference in NCCN and standard textbooks (DeVita's Cancer: Principles & Practice of Oncology). - **MAGIC Trial:** Established perioperative ECF (epirubicin + cisplatin + 5-FU), not purely adjuvant cisplatin + 5-FU. Cisplatin + 5-FU alone is a perioperative (neoadjuvant + adjuvant) regimen, not the standard *adjuvant-only* drug of choice. - Capecitabine monotherapy lacks robust level-1 evidence as a standalone adjuvant regimen in gastric cancer. - Paclitaxel monotherapy has no established role in adjuvant gastric cancer. ### Why 5-FU + Leucovorin is Correct Here | Criterion | Detail | |-----------|--------| | Trial support | INT-0116 (MacDonald) — level 1A evidence for adjuvant setting | | Setting | Post-curative (R0) resection, stage IB–III | | Regimen | 5-FU 425 mg/m² + Leucovorin 20 mg/m² × 5 days, repeated every 28 days with concurrent radiation | | Outcome | ~10-month improvement in median OS vs surgery alone | **High-Yield:** Among the four options listed, **5-FU + Leucovorin** is the only regimen with established level-1 evidence specifically in the *adjuvant* (post-resection) setting for gastric cancer (INT-0116/MacDonald trial). Cisplatin + 5-FU is used in the *perioperative* (MAGIC) context, not as a standalone adjuvant regimen. *(Reference: DeVita's Cancer: Principles & Practice of Oncology, 11th ed.; NCCN Gastric Cancer Guidelines 2023)* ### Clinical Pearl The MacDonald regimen (5-FU + Leucovorin ± radiation) remains the standard adjuvant approach in Western guidelines for resected gastric cancer. In Asian populations, S-1 or capecitabine + oxaliplatin (XELOX/CAPOX) are preferred, but among the options given, 5-FU + Leucovorin has the strongest evidence base.